Clinicopathologic significance of cathepsin B immunostaining in transitional neoplasia

Fifty Stage heterogeneous urinary bladder carcinomas were immunostained for cathepsin B, a lysosomal endoproteinase putatively associated with tumor invasion. Neoplastic cell CB immunoreactivity was strongly correlated to both grade (I/II--42% positive versus III--68% positive, P = 0.01) and invasion beyond the lamina propria (Ta/T1--42% positive versus T2/T3--68% positive, P = 0.02). Most low grade, papillary tumors displayed a granular cytoplasmic staining pattern, compatible with lysosomal distribution, in contrast to high grade tumors, in which diffuse staining was present in the cytoplasm. Staining was also accentuated at the advancing front of invading tumors and in angiolymphatic tumor emboli. Non-neoplastic mononuclear inflammatory cells, particularly those at the host-tumor interface, displayed variable, sometimes intense staining. Strong tumor-cell CB was more frequent among recurrent TCC than in patients who remain free of disease (55% versus 29%, n = 18, T2-3, cystectomy, 5-yr min. follow-up). We conclude these observed staining patterns and grade/stage associations are compatible with an important biological role for CB in facilitating host invasion in some bladder tumors. Levels and/or distribution of CB may also be of potential value in defining clinically aggressive tumor subsets.